Immunohistochemical detection of p53 protein accumulation in head and neck cancer: Correlation with p53 gene alterations

David Taylor, Wayne M. Koch, Marianna Zahurak, Keerti Shah, David Sidransky, William H. Westra

Research output: Contribution to journalArticlepeer-review

Abstract

The genetic and functional status of the p53 gene may be an important factor in guiding therapeutic strategies for patients with cancer. The purpose of this study was to determine whether p53 immunohistochemistry (IHC) accurately reflects the mutational status of the p53 gene and to determine whether p53 IHC independently predicts tumor responsiveness to radiation therapy for patients with HNSCC. p53 IHC was performed using the monoclonal antibody DO7 on tumors from 85 patients with HNSCC treated with primary or adjuvant radiation. The p55 status in all of these tumors was previously assessed by direct sequence analysis of exons 5 through 9: 49 tumors were p55 wild-type, and 36 harbored p53 gene mutations. All patients were well characterized with respect to locoregional recurrence, distant spread, and survival. Positive p53 staining was observed in 53 of the 85 cases (62%). Only 27 (51%) of these 53 IHC-positive cases harbored gene mutations in exons 5 through 9; 23 (72%) of the 32 IHC-negative cases did not harbor mutations. The overall correlation rate between IHC and sequencing was 59% (P < .04, χ2). Discordant results were observed for 35 (41%) cases, including 26 IHC- positive cases and 9 IHC-negative cases. In 7 of 9 cases, false-negative staining was due to a nonsense or splice-site mutation, p53 IHC was not predictive of overall survival (P = .37) or disease-free survival (P = .95). In a sizable number of cases, p53 IHC does not reflect the mutational status of the p53 gene. Specific types of alterations (eg, truncating mutations) and other factors may contribute to this poor correlation. Moreover, p53 IHC does not appear to be an independent predictor of tumor responsiveness to radiation in patients with HNSCC.

Original languageEnglish (US)
Pages (from-to)1221-1225
Number of pages5
JournalHuman pathology
Volume30
Issue number10
DOIs
StatePublished - Oct 1999

Keywords

  • E6
  • Head and neck squamons cell carcinoma
  • Human papilloma virus (HPV)
  • IHC
  • P53
  • Radiation therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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